Research

Drug Companion Diagnostics

Checkpoint Inhibitor Melanoma Trial

Study Design:

  • Metastatic melanoma, BRAF mutant patients, treated with experimental checkpoint inhibitor drugs.

Results:

  • Stratified patients into 3 cohorts (responsive, non-responsive, toxic).


Autoantibody Biomarker Discovery

Systemic Lupus Erythematosus (SLE)

Study Design:

  • Identification of novel autoantibodies in SLE and stratification of subgroups of SLE individuals.

Results:

  • 4 SLE subgroups were categorised based on hierarchical clustering and principal component analysis (PCA) with known autoantigens such as TROVE2 (Ro60) and SSB (La) forming a single cluster and novel TGF-β signalling (SMAD2 and SMAD5) and TLR signalling (My88) autoantigens forming another cluster.


Protein Interaction Assays

DNA-Protein Interaction Study

Study Design:

  • p53 microarray printed onto a neutravidin-derivatised dextran hydrogel surface probed with Cy3-labelled GADD45 duplex oligo

Results:

  • Quantitative parallel thermodynamic analysis revealed previously unknown functional effects of mutation on p53 protein-DNA interaction

  • Differential DNA binding activity of p53 mutant proteins

  • Quantitative analysis unravels mechanistic differences between ‘loss of function’ mutations 


Orvar™ Selection Technology

Colorectal Cancer

Study Design:

  • Sample type:
    • Plasma from Colorectal cancer and healthy normal individuals
    • Tissue from Colorectal cancer individuals (cancer and adjacent normal tissue)
  • Platform:
    • Sengenics KREX CT100+ microarray
    • Orvar™ Autoproteome™ Discovery technology

Results:

Breakdown of Selected/Identified Antigens

Figure 1: Distribution and classification of the top antigens identified in both experiments



  • Wild-type autoantigens – Matched positive results between Orvar™ and KREX microarray



  • Homologue autoantigens – Matched positive results between Orvar™ and KREX microarray



  • Autoantigens unique to Orvar™ – Autoantigens not found on KREX microarray



  • Non wild-type autoantigens – Positive results on Orvar™ only

  • The Orvar™ technology identified a total of 28 unique autoantigens (Figure 2) which had corresponding autoantibodies present in Colorectal cancer patients;
  • This Orvar™ Colorectal library also led to the discovery of homologues to the antigens eliciting high autoantibody responses on KREX microarrays. These homologues may contain overlapping surface epitopes reactive to these autoantibodies;
  • As all antigens immobilised onto the KREX microarrays are present as wild-type forms, the unique antigens on Orvar™ which are also on KREX microarrays suggests detection of mutated forms of these antigens using the Orvar™ technology.

Figure 2: GO enrichment analysis for the top 28 unique autoantigens identified using Orvar™

FEATURED PRODUCTS

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SARS-CoV-2 Antigens

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Sengenics - Functional Proteomics | Krex Technology | Protein Array Supplier

Sengenics is a functional proteomics company that leverages its patented KREX technology for production of full-length, correctly folded and functional proteins. The key application of KREX is the discovery of autoantibody biomarkers for two core medical use cases:  stratification of patients undergoing treatment with autoimmune or cancer drugs and identification of autoantibody biomarkers that may be used to diagnose cancer, autoimmune or neurodegenerative conditions. Some autoantibodies that are identified as diagnostic biomarkers may be protective and have potential in themselves as therapeutic biomolecules.

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